Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study
Authors: Betty Raman, Celeste McCracken, Mark P Cassar, Alastair J Moss, Lucy Finnigan, Azlan Helmy A Samat, Godwin Ogbole, Elizabeth M Tunnicliffe, Fidel Alfaro-Almagro, Ricarda Menke, Cheng Xie, Fergus Gleeson, Elena Lukaschuk, Hanan Lamlum, Kevin McGlynn, Iulia A Popescu, Zeena-Britt Sanders, Laura C Saunders, Stefan K Piechnik, Vanessa M Ferreira, Chrysovalantou Nikolaidou, Najib M Rahman, Ling-Pei Ho, Victoria C Harris, Aarti Shikotra, Amisha Singapuri, Paul Pfeffer, Charlotte Manisty, Onn M Kon, Mark Beggs, Declan P O'Regan, Jonathan Fuld, Jonathan R Weir-McCall, Dhruv Parekh, Rick Steeds, Krisnah Poinasamy, Dan J Cuthbertson, Graham J Kemp, Malcolm G Semple, Alexander Horsley, Christopher A Miller, Caitlin O'Brien, Ajay M Shah, Amedeo Chiribiri, Olivia C Leavy, Matthew Richardson, Omer Elneima, Hamish J C McAuley, Marco Sereno, Ruth M Saunders, Linzy Houchen-Wolloff, Neil J Greening, Charlotte E Bolton, Jeremy S Brown, Gourab Choudhury, Nawar Diar Bakerly, Nicholas Easom, Carlos Echevarria, Michael Marks, John R Hurst, Mark G Jones, Daniel G Wootton, Trudie Chalder, Melanie J Davies, Anthony De Soyza, John R Geddes, William Greenhalf, Luke S Howard, Joseph Jacob, William D-C Man, Peter J M Openshaw, Joanna C Porter, Matthew J Rowland, Janet T Scott, Sally J Singh, David C Thomas, Mark Toshner, Keir E Lewis, Liam G Heaney, Ewen M Harrison, Steven Kerr, Annemarie B Docherty, Nazir I Lone, Jennifer Quint, Aziz Sheikh, Bang Zheng, R Gisli Jenkins, Eleanor Cox, Susan Francis, Mark Halling-Brown, James D Chalmers, John P Greenwood, Sven Plein, Paul J C Hughes, A A Roger Thompson, Sarah L Rowland-Jones, James M Wild, Matthew Kelly, Thomas A Treibel, Steven Bandula, Raminder Aul, Karla Miller, Peter Jezzard, Stephen Smith, Thomas E Nichols, Gerry P McCann, Rachael A Evans, Louise V Wain, Christopher E Brightling, Stefan Neubauer, J K Baillie, Alison Shaw, Brigid Hairsine, Claire Kurasz, Helen Henson, Lisa Armstrong, Liz Shenton, H Dobson, Amanda Dell, Alice Lucey, Andrea Price, Andrew Storrie, Chris Pennington, Claire Price, Georgia Mallison, Gemma Willis, Heeah Nassa, Jill Haworth, Michaela Hoare, Nancy Hawkings, Sara Fairbairn, Susan Young, S Walker, I Jarrold, Amy Sanderson, C David, K Chong-James, O Zongo, W Y James, A Martineau, Bernie King, C Armour, D McAulay, E Major, Jade McGinness, L McGarvey, N Magee, Roisin Stone, S Drain, T Craig, A Bolger, Ahmed Haggar, Arwel Lloyd, Christian Subbe, Daniel Menzies, David Southern, Emma McIvor, K Roberts, R Manley, Victoria Whitehead, W Saxon, A Bularga, N L Mills, Hosni El-Taweel, Joy Dawson, Leanne Robinson, Dinesh Saralaya, Karen Regan, Kim Storton, Lucy Brear, S Amoils, Areti Bermperi, Anne Elmer, Carla Ribeiro, Isabel Cruz, Jessica Taylor, J Worsley, K Dempsey, L Watson, Sherly Jose, S Marciniak, M Parkes, Alison McQueen, Catherine Oliver, Jenny Williams, Kerry Paradowski, Lauren Broad, Lucy Knibbs, Matthew Haynes, Ramsey Sabit, L Milligan, Claire Sampson, Alyson Hancock, Cerys Evenden, Ceri Lynch, Kia Hancock, Lisa Roche, Meryl Rees, Natalie Stroud, T Thomas-Woods, S Heller, E Robertson, B Young, Helen Wassall, M Babores, Maureen Holland, Natalie Keenan, Sharlene Shashaa, Carly Price, Eva Beranova, Hazel Ramos, Heather Weston, Joanne Deery, Liam Austin, Reanne Solly, Sharon Turney, Tracey Cosier, Tracy Hazelton, M Ralser, Ann Wilson, Lorraine Pearce, S Pugmire, Wendy Stoker, W McCormick, A Dewar, Gill Arbane, G Kaltsakas, Helen Kerslake, J Rossdale, Karen Bisnauthsing, Laura A Aguilar Jimenez, L M Martinez, Marlies Ostermann, Murphy M Magtoto, Nicholas Hart, Philip Marino, Sarah Betts, Teresa S Solano, Ava Maria Arias, A Prabhu, Annabel Reed, Caroline Wrey Brown, Denise Griffin, Emily Bevan, Jane Martin, J Owen, Maria Alvarez Corral, Nick Williams, Sheila Payne, Will Storrar, Alison Layton, Cathy Lawson, Clare Mills, James Featherstone, Lorraine Stephenson, Tracy Burdett, Y Ellis, A Richards, C Wright, D L Sykes, K Brindle, Katie Drury, L Holdsworth, M G Crooks, Paul Atkin, Rachel Flockton, Susannah Thackray-Nocera, Abdelrahman Mohamed, Abigail Taylor, Emma Perkins, Gavin Ross, Heather McGuinness, Helen Tench, Janet Phipps, Ronda Loosley, Rebecca Wolf-Roberts, S Coetzee, Zohra Omar, Alexandra Ross, Bethany Card, Caitlin Carr, Clara King, Chloe Wood, D Copeland, Ellen Calvelo, Edwin R Chilvers, Emily Russell, Hussain Gordon, Jose Lloyd Nunag, J Schronce, Katherine March, Katherine Samuel, L Burden, Lynsey Evison, Laura McLeavey, Lorna Orriss-Dib, Lawrence Tarusan, Myril Mariveles, Maura Roy, Noura Mohamed, Neil Simpson, Najira Yasmin, P Cullinan, Patrick Daly, Sulaimaan Haq, Silvia Moriera, Tamanah Fayzan, Unber Munawar, Uchechi Nwanguma, A Lingford-Hughes, Danny Altmann, D Johnston, J Mitchell, J Valabhji, L Price, P L Molyneaux, Ryan S Thwaites, S Walsh, A Frankel, L Lightstone, M Wilkins, M Willicombe, S McAdoo, R Touyz, Anne-Marie Guerdette, Katie Warwick, Melanie Hewitt, R Reddy, Sonia White, A McMahon, Amy Hoare, Abigail Knighton, Albert Ramos, Amelie Te, Caroline J Jolley, Fabio Speranza, Hosanna Assefa-Kebede, Ida Peralta, Jonathon Breeze, K Shevket, Natassia Powell, Oluwaseun Adeyemi, Pearl Dulawan, Rita Adrego, S Byrne, Sheetal Patale, A Hayday, M Malim, C Pariante, C Sharpe, J Whitney, K Bramham, K Ismail, S Wessely, T Nicholson, Andrew Ashworth, Amy Humphries, Ai Lyn Tan, Beverley Whittam, C Coupland, Clair Favager, D Peckham, Elaine Wade, Gwen Saalmink, Jude Clarke, Jodie Glossop, Jennifer Murira, Jade Rangeley, Janet Woods, Lucy Hall, Matthhew Dalton, Nicola Window, Paul Beirne, Tim Hardy, G Coakley, Lance Turtle, Anthony Berridge, Andy Cross, Angela L Key, Anna Rowe, Ann Marie Allt, Chloe Mears, Flora Malein, Gladys Madzamba, H E Hardwick, Joanne Earley, Jenny Hawkes, James Pratt, J Wyles, K A Tripp, Kera Hainey, Lisa Allerton, L Lavelle-Langham, Lucy Melling, Lilian O Wajero, L Poll, Matthew J Noonan, N French, N Lewis-Burke, S A Williams-Howard, Shirley Cooper, Sabina Kaprowska, S L Dobson, Sophie Marsh, Victoria Highett, V Shaw, M Beadsworth, S Defres, Ekaterina Watson, Gerlynn F Tiongson, Padmasayee Papineni, Sambasivarao Gurram, Shalin N Diwanji, Sheena Quaid, A Briggs, Claire Hastie, Natalie Rogers, D Stensel, L Bishop, K McIvor, P Rivera-Ortega, B Al-Sheklly, Cristina Avram, David Faluyi, J Blaikely, K Piper Hanley, K Radhakrishnan, M Buch, N A Hanley, Natasha Odell, Rebecca Osbourne, Sue Stockdale, T Felton, T Gorsuch, T Hussell, Zunaira Kausar, T Kabir, H McAllister-Williams, S Paddick, D Burn, A Ayoub, Alan Greenhalgh, A Sayer, A Young, D Price, G Burns, G MacGowan, Helen Fisher, H Tedd, J Simpson, Kasim Jiwa, M Witham, Philip Hogarth, Sophie West, S Wright, Michael J McMahon, Paula Neill, Andrew Dougherty, A Morrow, David Anderson, D Grieve, Hannah Bayes, K Fallon, K Mangion, L Gilmour, N Basu, R Sykes, C Berry, I B McInnes, A Donaldson, E K Sage, Fiona Barrett, B Welsh, Murdina Bell, Jackie Quigley, Karen Leitch, L Macliver, Manish Patel, R Hamil, Andrew Deans, J Furniss, S Clohisey, Anne Elliott, A R Solstice, C Deas, Caroline Tee, David Connell, Debbie Sutherland, J George, S Mohammed, Jenny Bunker, Katie Holmes, A Dipper, Anna Morley, David Arnold, H Adamali, H Welch, Leigh Morrison, Louise Stadon, Nick Maskell, Shaney Barratt, Sarah Dunn, Samuel Waterson, Bhagy Jayaraman, Tessa Light, N Selby, A Hosseini, Karen Shaw, Paula Almeida, Robert Needham, Andrew K Thomas, Laura Matthews, Ayushman Gupta, Athanasios Nikolaidis, Catherine Dupont, J Bonnington, Melanie Chrystal, P L Greenhaff, S Linford, Sabrina Prosper, W Jang, Asma Alamoudi, Angela Bloss, Clare Megson, Debby Nicoll, Emily Fraser, Edmund Pacpaco, Florence Conneh, G Ogg, H McShane, Ivan Koychev, Jin Chen, John Pimm, Mark Ainsworth, M Pavlides, M Sharpe, May Havinden-Williams, Nayia Petousi, Nick Talbot, Penny Carter, Prathiba Kurupati, T Dong, Yanchun Peng, A Burns, N Kanellakis, A Korszun, B Connolly, J Busby, T Peto, B Patel, C M Nolan, Daniele Cristiano, J A Walsh, Kamal Liyanage, Mahitha Gummadi, N Dormand, Oliver Polgar, P George, R E Barker, Suhani Patel, L Price, M Gibbons, Darwin Matila, Hannah Jarvis, Lai Lim, Olaoluwa Olaosebikan, Shanaz Ahmad, Simon Brill, S Mandal, C Laing, Alice Michael, A Reddy, C Johnson, H Baxendale, H Parfrey, J Mackie, J Newman, Jamie Pack, J Parmar, K Paques, Lucie Garner, Alice Harvey, C Summersgill, D Holgate, E Hardy, J Oxton, Jessica Pendlebury, L McMorrow, N Mairs, N Majeed, P Dark, R Ugwuoke, Sean Knight, S Whittaker, Sophia Strong-Sheldrake, Wadzanai Matimba-Mupaya, P Chowienczyk, Dibya Pattenadk, E Hurditch, Flora Chan, H Carborn, H Foot, J Bagshaw, J Hockridge, J Sidebottom, Ju Hee Lee, K Birchall, Kim Turner, L Haslam, L Holt, L Milner, M Begum, M Marshall, N Steele, N Tinker, Phillip Ravencroft, Robyn Butcher, S Misra, S Walker, Zach Coburn, Alexandra Fairman, Amber Ford, Ailsa Holbourn, Alice Howell, Allan Lawrie, Alison Lye, Angeline Mbuyisa, Amira Zawia, B Holroyd-Hind, B Thamu, Cameron Clark, Claire Jarman, C Norman, C Roddis, David Foote, Elvina Lee, F Ilyas, G Stephens, Helen Newell, Helena Turton, Irene Macharia, Imogen Wilson, Joby Cole, J McNeill, J Meiring, J Rodger, James Watson, Kerry Chapman, Kate Harrington, Luke Chetham, L Hesselden, Lorenza Nwafor, Myles Dixon, Megan Plowright, Phillip Wade, Rebecca Gregory, Rebecca Lenagh, R Stimpson, Sharon Megson, Tom Newman, Yutung Cheng, Camelia Goodwin, Cheryl Heeley, D Sissons, D Sowter, Heidi Gregory, Inez Wynter, John Hutchinson, Jill Kirk, Kaytie Bennett, Katie Slack, Lynne Allsop, Leah Holloway, Margaret Flynn, Mandy Gill, M Greatorex, Megan Holmes, Phil Buckley, Sarah Shelton, Sarah Turner, Terri Ann Sewell, V Whitworth, Wayne Lovegrove, Johanne Tomlinson, Louise Warburton, Sharon Painter, Carinna Vickers, Dawn Redwood, Jo Tilley, Sue Palmer, Tania Wainwright, G Breen, M Hotopf, A Dunleavy, J Teixeira, Mariam Ali, Mark Mencias, N Msimanga, Sulman Siddique, T Samakomva, Vera Tavoukjian, D Forton, R Ahmed, Amanda Cook, Favas Thaivalappil, Lynda Connor, Tabitha Rees, M McNarry, N Williams, Jacqueline McCormick, Jerome McIntosh, Joanne Vere, Martina Coulding, Susan Kilroy, Victoria Turner, Al-Tahoor Butt, Heather Savill, Eva Fraile, Jacinta Ugoji, G Landers, Harpreet Lota, Sofiya Portukhay, Mariam Nasseri, Alison Daniels, Anil Hormis, Julie Ingham, Lisa Zeidan, Lynn Osborne, Manish Chablani, A Banerjee, A David, A Pakzad, B Rangelov, B Williams, E Denneny, J Willoughby, M Xu, P Mehta, R Batterham, R Bell, S Aslani, W Lilaonitkul, A Checkley, Dongchun Bang, Donna Basire, D Lomas, E Wall, Hannah Plant, K Roy, M Heightman, M Lipman, Marta Merida Morillas, Nyarko Ahwireng, R C Chambers, Roman Jastrub, S Logan, T Hillman, A Botkai, A Casey, A Neal, A Newton-Cox, B Cooper, C Atkin, C McGee, C Welch, D Wilson, E Sapey, H Qureshi, J Hazeldine, J M Lord, J Nyaboko, J Short, J Stockley, J Dasgin, K Draxlbauer, K Isaacs, K Mcgee, K P Yip, L Ratcliffe, M Bates, M Ventura, N Ahmad Haider, N Gautam, R Baggott, S Holden, S Madathil, S Walder, S Yasmin, T Hiwot, T Jackson, T Soulsby, V Kamwa, Z Peterkin, Z Suleiman, N Chaudhuri, H Wheeler, R Djukanovic, R Samuel, T Sass, T Wallis, B Marshall, C Childs, E Marouzet, M Harvey, S Fletcher, C Dickens, P Beckett, U Nanda, E Daynes, A Charalambou, A J Yousuf, A Lea, A Prickett, Bibek Gooptu, Beverley Hargadon, Charlotte Bourne, C Christie, C Edwardson, D Lee, E Baldry, E Stringer, F Woodhead, G Mills, H Arnold, H Aung, I N Qureshi, J Finch, J Skeemer, K Hadley, Kamlesh Khunti, Liesel Carr, L Ingram, M Aljaroof, M Bakali, M Bakau, M Baldwin, Michelle Bourne, Manish Pareek, M Soares, Martin Tobin, Natalie Armstrong, Nigel Brunskill, N Goodman, P Cairns, Pranab Haldar, P McCourt, R Dowling, Richard Russell, Sarah Diver, Sarah Edwards, Sarah Glover, S Parker, Salman Siddiqui, T J C Ward, T Mcnally, T Thornton, Tom Yates, W Ibrahim, Will Monteiro, D Thickett, D Wilkinson, M Broome, P McArdle, R Upthegrove, D Wraith, C Langenberg, C Summers, E Bullmore, J L Heeney, W Schwaeble, C L Sudlow, D Adeloye, D E Newby, I Rudan, M Shankar-Hari, M Thorpe, R Pius, S Walmsley, A McGovern, C Ballard, L Allan, J Dennis, J Cavanagh, J Petrie, K O'Donnell, M Spears, N Sattar, S MacDonald, E Guthrie, M Henderson, Beatriz Guillen Guio, Bang Zhao, C Lawson, Charlotte Overton, Chris Taylor, C Tong, Elizabeta Mukaetova-Ladinska, E Turner, John E Pearl, J Sargant, J Wormleighton, Michelle Bingham, M Sharma, Mike Steiner, Nilesh Samani, Petr Novotny, Rob Free, R J Allen, Selina Finney, Sarah Terry, Terry Brugha, Tatiana Plekhanova, A McArdle, B Vinson, L G Spencer, W Reynolds, M Ashworth, B Deakin, H Chinoy, K Abel, M Harvie, S Stanel, A Rostron, C Coleman, D Baguley, E Hufton, F Khan, I Hall, I Stewart, L Fabbri, L Wright, P Kitterick, R Morriss, S Johnson, A Bates, C Antoniades, D Clark, K Bhui, K M Channon, K Motohashi, L Sigfrid, M Husain, M Webster, X Fu, X Li, L Kingham, P Klenerman, K Miiler, G Carson, G Simons, N Huneke, P C Calder, D Baldwin, S Bain, D Lasserson, L Daines, E Bright, M Stern, P Crisp, R Dharmagunawardena, A Reddington, A Wight, L Bailey, A Ashish, E Robinson, J Cooper, A Broadley, A Turnbull, C Brookes, C Sarginson, D Ionita, H Redfearn, K Elliott, L Barman, L Griffiths, Z Guy, Rhyan Gill, Rashmita Nathu, Edward Harris, P Moss, J Finnigan, Kathryn Saunders, Peter Saunders, S Kon, Samantha S Kon, Linda O'Brien, K Shah, P Shah, Emma Richardson, V Brown, M Brown, Jo Brown, J Brown, Ammani Brown, Angela Brown, M Brown, N Choudhury, S Jones, H Jones, L Jones, I Jones, G Jones, Heather Jones, Don Jones, Ffyon Davies, Ellie Davies, Kim Davies, Gareth Davies, Gwyneth A Davies, K Howard, Julie Porter, J Rowland, A Rowland, Kathryn Scott, Suver Singh, Claire Singh, S Thomas, Caradog Thomas, Victoria Lewis, J Lewis, D Lewis, P Harrison, C Francis, R Francis, Rachel Ann Hughes, Joan Hughes, A D Hughes, T Thompson, S Kelly, D Smith, Nikki Smith, Andrew Smith, Jacqui Smith, Laurie Smith, Susan Smith, Teriann Evans, Ranuromanana I Evans, D Evans, R Evans, H Evans, J Evans
Journal: The Lancet Respiratory Medicine (2023)

<h2>Summary</h2><h3>Introduction</h3> The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. <h3>Methods</h3> In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. <h3>Findings</h3> Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 <i>vs</i> 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; p<sub>adjusted</sub>=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities <i>vs</i> mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; p<sub>adjusted</sub>=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; p<sub>adjusted</sub>=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. <h3>Interpretation</h3> After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification. <h3>Funding</h3> UK Research and Innovation and National Institute for Health Research.